Primary drug delivery methods include oral delivery and injections, but both methods present difficulties. For instance, injections are painful and both methods tend to provide bursts of agents rather than a preferred steady-state delivery. Additionally, the successful long term use of both oral delivery and injected delivery requires the patient to consistently meet the time requirements for the delivery method.
Transdermal delivery materials have been developed in an attempt to provide a painless route for delivery of active agents over a sustained period with little or no interruption of the patient's daily routine. Unfortunately, natural dermal characteristics such as the overlapping corneocytes of the stratum corneum, the tight junction of the stratum granulosum, and Langerhans cells of the stratum spinosum that institute an immune response and/or a foreign body response all present barriers to successful transdermal delivery of an active agent.
The utilization of microneedles to facilitate transdermal delivery of active agents has improved this delivery route. A microneedle transdermal device includes an array of needles that may penetrate at least the stratum corneum and reach an underlying layer of the skin. In some devices, the microneedles are designed so as to penetrate to a depth that does not stimulate the nerve endings and institute a pain response. Examples of microneedle devices have been described in U.S. Pat. No. 6,334,856 to Allen, et al. and U.S. Pat. No. 7,226,439 to Prausnitz, et al., both of which are incorporated herein by reference.
In order to take full advantage of microneedle devices, efficient methods for mass production of devices that may deliver a wide array of agents need to be developed. Attempts have been made to form microneedle arrays by injection molding processes. For instance, U.S. Patent Application Publication No. 2007/0191761 to Boone, et al. describes a method including injecting a moldable material into a negative mold insert that is characterized by a negative image of a microneedle. U.S. patent Application Publication No. 2008/0088066 to Ferguson, et al. describes a method that utilizes a mold apparatus including a mold insert that has a negative image of a microneedle and a compression core. The mold housing allows reciprocal motion between the mold insert and the compression core and when the housing is in a closed position, a polymeric material is injected into the closed apparatus.
Unfortunately, even with the inclusion of injection molded microneedles, transdermal devices are presently limited to delivery of low molecular weight agents that have a moderate lipophilicity and no charge. Even upon successful crossing of the natural dermal boundary, problems still exist with regard to maintaining the activity level of delivered agents and avoidance of foreign body and immune response.
What are needed in the art are microneedle devices that may be utilized for delivery of a wide variety of agents, including high molecular weight agents. What is also needed in the art is an efficient method for forming the devices that may be translated to a mass production facility, such as an injection molding method.